RESUMEN
Human antibodies generated by Epstein-Barr virus immortalized B-cells from tumor-draining lymph nodes of an ovarian cancer patient were screened for reactivity in enzyme-linked immunosorbent assay with a synthetic peptide corresponding to the protein core of the polymorphic epithelial mucin. Epitopes within this region are in fact considered tumor specific since they are selectively exposed in tumor cells due to aberrant glycosylation. Human antibody BB5, thus selected, reacts in enzyme-linked immunosorbent assay and immunohistochemistry with polymorphic epithelial mucin-expressing tumor cells. This is the first demonstration of the existence of a B-cell immune response to selected epitopes of polymorphic epithelial mucin and, together with the cytotoxic T-cell response already demonstrated, constitutes the basis for the use of synthetic peptides as a vaccine in cancer patients.
Asunto(s)
Anticuerpos Antineoplásicos/análisis , Linfocitos B/inmunología , Glicoproteínas de Membrana/inmunología , Mucinas/inmunología , Neoplasias Ováricas/inmunología , Adulto , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Línea Celular Transformada , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunidad Celular , Glicoproteínas de Membrana/química , Datos de Secuencia Molecular , Mucina-1 , Mucinas/química , Neoplasias Ováricas/patología , Células Tumorales CultivadasRESUMEN
Two tumor lines derived from 3LL (Lewis lung carcinoma) endowed with different metastatic potential and stable for their metastatic phenotype during serial in vivo passages, have been analysed for growth and dissemination following treatment with a monoclonal antibody. We have used a recently developed MoAb 135-13C to a tumor-associated antigen of murine lung carcinoma having an apparent molecular weight of 180,000 (TSP-180). The metastatic dissemination of the 3LL variants before and after treatment with the MoAb has been correlated with the expression on the cell surface of the MHC antigens (Db, Kb) and of the TSP-180 protein. The results of this study indicate that cell with high TSP-180 protein expression and MHC antigen expression have the greatest metastatic potential. Administration of MoAb 135-13C to tumor-bearing mice or i.v. injection of cells preincubated with the MoAb 135-13C increase the dissemination capacity of the variant endowed with lower metastatic potential while inducing a reverse effect on the high metastatic one. Studies on the MHC expression demonstrate that MoAb 135-13C treatment induces changes in the Db and Kb expression at level of secondary neoplasms. The results are discussed in view of the importance of the use of the metastatic variants to study therapeutic effect of specific targeting agent.